1. Medullipin I (Med I) is a hormone extracted from renal papillae and its renomedullary interstitial cells (RIC). Med I is stimulated by elevation of the renal artery perfusion pressure. 2. When isolated normal rat kidneys were perfused either with oxygenated blood or with 5% albumin bubbled with O2 at elevated perfusion pressures, Med I appeared to be secreted into the renal venous effluent (RVE). Addition of Tween 20, treatment of the assay rat with SKF 525A, inhibitor of cytochrome P-450 and removal of the liver from the systemic circulation prevented vasodepression of both the RVE and extracted Med I. The lipid in the RVE gave the same dose-response as extracted Med I. 3. Lowering the renal artery perfusion pressure below normal inhibited the secretion of Med I. As the perfusion pressure was elevated Med I secretion appeared to increase. 4. Previous observations and the present study support the view that the renin-angiotensin system and the Medullipin system are double feedback systems involved in blood pressure control.